NCI Protocol(s): 10075 ?A Phase 1B Study of AMG-232 in Combination with Decitabine in Acute Myeloid Leukemia? and 10076 ?A Phase 1 Dose-Escalation and Exploratory Dose Expansion Study of AMG 232 in Combination with Carfilzomib, Lenalidomide, and Dexamethasone in Relapsed and/or Refractory Myeloma? (10075) Gene sequencing studies have shown that, on average, de novo AML cases contain more than 10 significant gene mutations, many of which can be broadly grouped into nine categories of genes thought to effect leukemogenesis: DNA-methylation, tumor suppression, transcription-factor fusions, nucleophosmin, signaling, chromatin-modification, myeloid transcription factor, the cohesin complex, and the spliceosome complex. This contract will provide for a comprehensive mutation panel (ASXL1, TET2, PHF6, DNMT3A, IDH1/2, FLT3, NPM1, KIT, miR-29b, FLT3-ITD, CEBPA, and MLL-PTD) to be performed on AML blasts collected from all patients when they undergo screening for enrollment eligibility in the trial. (10076) MIC-1, a secreted protein that is strongly induced by activated p53, can be detected in the peripheral blood following MDM2 inhibition. Therefore, MIC-1 could have utility as a pharmacodynamic biomarker for AMG 232. MIC-1 level can be determined by a sensitive ELISA test, and if correlated with dose or other pharmacodynamic effects, can serve as a serum biomarker for p53 activation. We anticipate that most subjects treated with AMG 232 will have an induction in MIC-1 and that the level of MIC-1 induction will be correlated with the dose of AMG 232 and the combination with KRd. A commercially available ELISA kit will be utilized to measure serum MIC-1 levels. This is for an integrated assay aimed at assessing drug response in subjects on the clinical trial and will be utilized to determine serum MIC-1 concentrations and ultimately the drug response. The post-treatment MIC-1 level will be normalized to the baseline level for that subject. In preliminary analyses of clinical trial data, there was an exposure-response correlation observed between changes in serum MIC-1 levels and AMG 232 exposure (both maximal (Cmax) and total exposure (AUC).